MCAM is a novel opioid antagonist whose advantages over naloxone for opioid overdose include a pseudo-irreversible interaction with the opioid receptor, and a much longer duration of action. These attributes indicate better reversal of the respiratory depressant effects of very potent and/or very long lasting opioid receptor agonists and better treatment of opioid use disorder. Proof-of-concept studies in non human primates demonstrate MCAM?s long duration of action against the reinforcing and respiratory-depressant effects of remifentanil and heroin, respectively. Doses of MCAM that were 10 times larger than those that protected against the effects of mu opioid receptor agonists had no effect on food-maintained responding in rhesus monkeys, and did not modify blood pressure, heart rate or body temperature. This proposal seeks funding for composition and study of the pharmacodynamics of MCAM (UG3 portion). In the UH3 portion, GMP-MCAM will be studied in additional pharmacodynamics assays and animal toxicity and safety studies. An IND application, following consultation with the FDA will be sought using these data. Contract Research Organizations have been identified for each stage of the proposal. The proposal describes the necessary and sufficient conditions from which to establish MCAM?s safety and antagonist activity in animals and humans. MCAM may be able to prevent all actions of any ?-receptor opioid drug in humans for a longer period of time than any other antagonist given acutely. MCAM offers potential therapeutic objectives that are not achieved with any other drug. The successful execution of this proposal will establish these claims.